scholarly journals Synaptic Properties and Plasticity Mechanisms of Invertebrate Tonic and Phasic Neurons

2020 ◽  
Vol 11 ◽  
Author(s):  
Nicole A. Aponte-Santiago ◽  
J. Troy Littleton
Keyword(s):  
Neuronal Cell ◽  
Cell Types ◽  
Brain Cell ◽  
Important Goal ◽  
Transient Responses ◽  
Short Term ◽  
Synaptic Release ◽  
Related Cell ◽  
Firing Characteristics ◽  
Broad Classification

Defining neuronal cell types and their associated biophysical and synaptic diversity has become an important goal in neuroscience as a mechanism to create comprehensive brain cell atlases in the post-genomic age. Beyond broad classification such as neurotransmitter expression, interneuron vs. pyramidal, sensory or motor, the field is still in the early stages of understanding closely related cell types. In both vertebrate and invertebrate nervous systems, one well-described distinction related to firing characteristics and synaptic release properties are tonic and phasic neuronal subtypes. In vertebrates, these classes were defined based on sustained firing responses during stimulation (tonic) vs. transient responses that rapidly adapt (phasic). In crustaceans, the distinction expanded to include synaptic release properties, with tonic motoneurons displaying sustained firing and weaker synapses that undergo short-term facilitation to maintain muscle contraction and posture. In contrast, phasic motoneurons with stronger synapses showed rapid depression and were recruited for short bursts during fast locomotion. Tonic and phasic motoneurons with similarities to those in crustaceans have been characterized in Drosophila, allowing the genetic toolkit associated with this model to be used for dissecting the unique properties and plasticity mechanisms for these neuronal subtypes. This review outlines general properties of invertebrate tonic and phasic motoneurons and highlights recent advances that characterize distinct synaptic and plasticity pathways associated with two closely related glutamatergic neuronal cell types that drive invertebrate locomotion.

scholarly journals An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types

2020 ◽  
Author(s):  
Zizhen Yao ◽  
Hanqing Liu ◽  
Fangming Xie ◽  
Stephan Fischer ◽  
A. Sina Booeshaghi ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Single Cell ◽  
Primary Motor Cortex ◽  
Neuronal Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Brain Cell ◽  
Molecular Signatures ◽  
Sequencing Technologies ◽  
Cell Transcriptome

AbstractSingle cell transcriptomics has transformed the characterization of brain cell identity by providing quantitative molecular signatures for large, unbiased samples of brain cell populations. With the proliferation of taxonomies based on individual datasets, a major challenge is to integrate and validate results toward defining biologically meaningful cell types. We used a battery of single-cell transcriptome and epigenome measurements generated by the BRAIN Initiative Cell Census Network (BICCN) to comprehensively assess the molecular signatures of cell types in the mouse primary motor cortex (MOp). We further developed computational and statistical methods to integrate these multimodal data and quantitatively validate the reproducibility of the cell types. The reference atlas, based on more than 600,000 high quality single-cell or -nucleus samples assayed by six molecular modalities, is a comprehensive molecular account of the diverse neuronal and non-neuronal cell types in MOp. Collectively, our study indicates that the mouse primary motor cortex contains over 55 neuronal cell types that are highly replicable across analysis methods, sequencing technologies, and modalities. We find many concordant multimodal markers for each cell type, as well as thousands of genes and gene regulatory elements with discrepant transcriptomic and epigenomic signatures. These data highlight the complex molecular regulation of brain cell types and will directly enable design of reagents to target specific MOp cell types for functional analysis.

scholarly journals An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

2020 ◽  
Author(s):  
Yang Eric Li ◽  
Sebastian Preissl ◽  
Xiaomeng Hou ◽  
Ziyang Zhang ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Target Genes ◽  
Adult Mouse ◽  
Neuronal Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Brain Regions ◽  
Brain Cell ◽  
Mammalian Brain ◽  
Cell Type ◽  
Gene Regulatory

ABSTRACTThe mammalian cerebrum performs high level sensory, motor control and cognitive functions through highly specialized cortical networks and subcortical nuclei. Recent surveys of mouse and human brains with single cell transcriptomics1–3 and high-throughput imaging technologies4,5 have uncovered hundreds of neuronal cell types and a variety of non-neuronal cell types distributed in different brain regions, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each brain cell type have yet to be elucidated. Here, we probe the accessible chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to define 491,818 candidate cis regulatory DNA elements in 160 distinct sub-types. We link a significant fraction of them to putative target genes expressed in diverse cerebral cell types and uncover transcriptional regulators involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of non-coding risk variants associated with various neurological disease and traits in humans. To facilitate the dissemination of information, we have set up a web portal (http://catlas.org/mousebrain).

scholarly journals Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson’s disease heritability

2018 ◽  
Author(s):  
Regina H Reynolds ◽  
Juan Botía ◽  
Mike A Nalls ◽  
John Hardy ◽  
Sarah A Gagliano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Types ◽  
Brain Regions ◽  
Brain Cell ◽  
Specific Gene ◽  
Specific Cell ◽  
Cell Type ◽  
Related Cell ◽  
Cell Type Specific

AbstractParkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set specifically expressed in astrocytic and microglial subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes to which cell types may have varying vulnerability.

scholarly journals Genetic mapping of etiologic brain cell types for obesity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Pascal N Timshel ◽  
Jonatan J Thompson ◽  
Tune H Pers
Keyword(s):  
Genome Wide Association Study ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Cell ◽  
Gwas Data ◽  
Sensory Stimuli ◽  
Genome Wide ◽  
Pretectal Nucleus ◽  
System Cell ◽  
Novel Strategy

The underlying cell types mediating predisposition to obesity remain largely obscure. Here, we integrated recently published single-cell RNA-sequencing (scRNA-seq) data from 727 peripheral and nervous system cell types spanning 17 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >457,000 individuals. Developing a novel strategy for integrating scRNA-seq data with GWAS data, we identified 26, exclusively neuronal, cell types from the hypothalamus, subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched for BMI heritability (p<1.6×10−4). Using genes harboring coding mutations associated with obesity, we replicated midbrain cell types from the anterior pretectal nucleus and periaqueductal gray (p<1.2×10−4). Together, our results suggest that brain nuclei regulating integration of sensory stimuli, learning and memory are likely to play a key role in obesity and provide testable hypotheses for mechanistic follow-up studies.

scholarly journals Mapping heritability of obesity by brain cell types

2020 ◽  
Author(s):  
Pascal N Timshel ◽  
Jonatan J Thompson ◽  
Tune H Pers
Keyword(s):  
Energy Homeostasis ◽  
Genome Wide Association Study ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Cell ◽  
Gwas Data ◽  
Steroidogenic Factor 1 ◽  
Sensory Stimuli ◽  
Pretectal Nucleus ◽  
Novel Strategy

The underlying cell types mediating predisposition to obesity remain largely obscure. Here we first integrated recently published single-cell RNA-sequencing (scRNA-seq) data from >380 peripheral and nervous system cell types spanning 19 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >450,000 individuals. Leveraging a novel strategy for integrating scRNA-seq data with GWAS data, we identified 22, exclusively neuronal, cell types from the subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched for BMI heritability (P<1.6×10-4). Using genes harboring coding mutations leading to syndromic forms of obesity, we replicate four midbrain cell types from the anterior pretectal nucleus, superior nucleus, periaqueductal gray and pallidum (P<1.7×10-4). Testing an additional set of 347 hypothalamic cell types, ventromedial hypothalamic steroidogenic-factor 1 (SF1) and cholecystokinin b receptor (CCKBR)-expressing neurons (P=4.9×10-5) previously implicated in energy homeostasis and glucose control and three cell types from the preoptic area of the hypothalamus and the lateral hypothalamus enriched for BMI GWAS associations (P<4.9×10-5). Together, our results suggest brain nuclei regulating integration of sensory stimuli, learning and memory are likely to play a key role in obesity and provide testable hypotheses for mechanistic follow-up studies.

NeuN, a neuronal specific nuclear protein in vertebrates

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 201-211 ◽  
Author(s):  
R.J. Mullen ◽  
C.R. Buck ◽  
A.M. Smith
Keyword(s):  
Nervous System ◽  
Nuclear Protein ◽  
Neuronal Cell ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Brain Cell ◽  
Cell Nuclei ◽  
Neuronal Nuclei ◽  
Specific Nuclear Protein

A battery of monoclonal antibodies (mAbs) against brain cell nuclei has been generated by repeated immunizations. One of these, mAb A60, recognizes a vertebrate nervous system- and neuron-specific nuclear protein that we have named NeuN (Neuronal Nuclei). The expression of NeuN is observed in most neuronal cell types throughout the nervous system of adult mice. However, some major cell types appear devoid of immunoreactivity including cerebellar Purkinje cells, olfactory bulb mitral cells, and retinal photoreceptor cells. NeuN can also be detected in neurons in primary cerebellar cultures and in retinoic acid-stimulated P19 embryonal carcinoma cells. Immunohistochemically detectable NeuN protein first appears at developmental timepoints which correspond with the withdrawal of the neuron from the cell cycle and/or with the initiation of terminal differentiation of the neuron. NeuN is a soluble nuclear protein, appears as 3 bands (46-48 × 10(3) M(r)) on immunoblots, and binds to DNA in vitro. The mAb crossreacts immunohistochemically with nervous tissue from rats, chicks, humans, and salamanders. This mAb and the protein recognized by it serve as an excellent marker for neurons in the central and peripheral nervous systems in both the embryo and adult, and the protein may be important in the determination of neuronal phenotype.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

scholarly journals The landscape of alternative polyadenylation in single cells of the developing mouse embryo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikram Agarwal ◽  
Sereno Lopez-Darwin ◽  
David R. Kelley ◽  
Jay Shendure
Keyword(s):  
Rna Binding ◽  
Developmental Stages ◽  
Single Cells ◽  
Neuronal Cell ◽  
Alternative Polyadenylation ◽  
Cell Types ◽  
Untranslated Regions ◽  
Mammalian Development ◽  
Translation Rate ◽  
Dynamic Landscape

Abstract3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.

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